Insulin, Glucagon and Blood Glucose

Since diabetes is a disease that affects your body's ability to use glucose, let's start by looking at what glucose is and how your body controls it. Glucose is a simple sugar that provides energy to all of the cells in your body. The cells take in glucose from the blood and break it down for energy (some cells, like brain cells and red blood cells, rely solely on glucose for fuel). The glucose in the blood comes from the food that you eat.

A glucose molecule

When you eat food, glucose gets absorbed from your intestines and distributed by the bloodstream to all of the cells in your body. Your body tries to keep a constant supply of glucose for your cells by maintaining a constant glucose concentration in your blood -- otherwise, your cells would have more than enough glucose right after a meal and starve in between meals and overnight. So, when you have an oversupply of glucose, your body stores the excess in the liver and muscles by making glycogen, long chains of glucose. When glucose is in short supply, your body mobilizes glucose from stored glycogen and/or stimulates you to eat food. The key is to maintain a constant blood-glucose level.

To maintain a constant blood-glucose level, your body relies on two hormones produced in the pancreas that have opposite actions: insulin and glucagon.

The pancreas has many islets that contain insulin-producing beta cells and glucagon-producing alpha cells.

Pancreas Your pancreas is located on the left side of your body, in the abdomen below your stomach. It produces many digestive enzymes that break down food (exocrine function) and hormones (endocrine function) that regulate blood glucose.

Insulin is made and secreted by the beta cells of the pancreatic islets, small islands of endocrine cells in the pancreas. Insulin is a protein hormone that contains 51 amino acids. Insulin is required by almost all of the body's cells, but its major targets are liver cells, fat cells and muscle cells. For these cells, insulin does the following:

• Stimulates liver and muscle cells to store glucose in glycogen
• Stimulates fat cells to form fats from fatty acids and glycerol
• Stimulates liver and muscle cells to make proteins from amino acids
• Inhibits the liver and kidney cells from making glucose from intermediate compounds of metabolic pathways (gluconeogenesis)

As such, insulin stores nutrients right after a meal by reducing the concentrations of glucose, fatty acids and amino acids in the bloodstream.

Insulin and glucagon have opposite effects on liver and other tissues for controlling blood-glucose levels.

Glucagon At very high concentrations, generally above the maximum levels found in the body, glucagon can act on fat cells to break down fats into fatty acids and glycerol, releasing the fatty acids into the bloodstream. However, this is a pharmacological effect, not a physiological one.

So, what happens when you do not eat? In times of fasting, your pancreas releases glucagon so that your body can produce glucose. Glucagon is another protein hormone that is made and secreted by the alpha cells of the pancreatic islets. Glucagon acts on the same cells as insulin, but has the opposite effects:

• Stimulates the liver and muscles to break down stored glycogen (glycogenolysis) and release the glucose
• Stimulates gluconeogenesis in the liver and kidneys

In contrast to insulin, glucagon mobilizes glucose from stores inside your body and increases the concentrations of glucose in the bloodstream -- otherwise, your blood glucose would fall to dangerously low levels.

Photo courtesy Eli Lilly & Company Insulin is what diabetics lack -- and what they need for treatment.

So how does your body know when to secrete glucagon or insulin? Normally, the levels of insulin and glucagon are counter-balanced in the bloodstream. For example, just after you eat a meal, your body is ready to receive the glucose, fatty acids and amino acids absorbed from the food. The presence of these substances in the intestine stimulates the pancreatic beta cells to release insulin into the blood and inhibit the pancreatic alpha cells from secreting glucagon. The levels of insulin in the blood begin to rise and act on cells (particularly liver, fat and muscle) to absorb the incoming molecules of glucose, fatty acids and amino acids. This action of insulin prevents the blood-glucose concentration (as well as the concentrations of fatty acids and amino acids) from substantially increasing in the bloodstream. In this way, your body maintains a steady blood-glucose concentration in particular.

In contrast, when you are between meals or sleeping, your body is essentially starving. Your cells need supplies of glucose from the blood in order to keep going. During these times, slight drops in blood-sugar levels stimulate glucagon secretion from the pancreatic alpha cells and inhibit insulin secretion from the beta cells. Blood-glucagon levels rise. Glucagon acts on liver, muscle and kidney tissue to mobilize glucose from glycogen or to make glucose that gets released into the blood. This action prevents the blood-glucose concentration from falling drastically.

As you can see, the interplay between insulin and glucagon secretions throughout the day help to keep your blood-glucose concentration constant, staying at about 90 mg per 100 ml of blood (5 millimolar).

Glucose Tolerance Test A Glucose Tolerance Test is a diagnostic test for diabetes. After fasting overnight, you are given a concentrated sugar solution (50 to 100 grams of glucose) to drink, and your blood is sampled periodically over the next several hours to test its glucose levels. Normally, blood glucose does not rise very much and returns to normal within two to three hours. In a diabetic, the blood glucose is usually higher after fasting, rises more after the glucose solution and takes from four to six hours to come down.